Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, Mail Code 8904, 1210 Amsterdam Avenue, New York, New York 10027, USA.
J Acoust Soc Am. 2011 Nov;130(5):3059-67. doi: 10.1121/1.3646905.
The activation of bubbles by an acoustic field has been shown to temporarily open the blood-brain barrier (BBB), but the trigger cause responsible for the physiological effects involved in the process of BBB opening remains unknown. Here, the trigger cause (i.e., physical mechanism) of the focused ultrasound-induced BBB opening with monodispersed microbubbles is identified. Sixty-seven mice were injected intravenously with bubbles of 1-2, 4-5, or 6-8 μm in diameter and the concentration of 10(7) numbers/ml. The right hippocampus of each mouse was then sonicated using focused ultrasound (1.5 MHz frequency, 100 cycles pulse length, 10 Hz pulse repetition frequency, 1 min duration). Peak-rarefactional pressures of 0.15, 0.30, 0.45, or 0.60 MPa were applied to identify the threshold of BBB opening and inertial cavitation (IC). Our results suggest that the BBB opens with nonlinear bubble oscillation when the bubble diameter is similar to the capillary diameter and with inertial cavitation when it is not. The bubble may thus have to be in contact with the capillary wall to induce BBB opening without IC. BBB opening was shown capable of being induced safely with nonlinear bubble oscillation at the pressure threshold and its volume was highly dependent on both the acoustic pressure and bubble diameter.
声场激活气泡已被证明可以暂时打开血脑屏障（BBB），但涉及 BBB 开放过程中生理效应的触发原因仍不清楚。本文确定了单分散微泡聚焦超声诱导 BBB 开放的触发原因（即物理机制）。将直径为 1-2、4-5 或 6-8μm 且浓度为 10（7）个/ml 的气泡静脉内注射到 67 只小鼠中。然后使用聚焦超声（1.5MHz 频率、100 个脉冲长度、10Hz 脉冲重复频率、1 分钟持续时间）对每只小鼠的右海马体进行声处理。施加 0.15、0.30、0.45 或 0.60MPa 的峰值稀疏压力，以确定 BBB 开放和惯性空化（IC）的阈值。我们的结果表明，当气泡直径与毛细血管直径相同时，BBB 会随着非线性气泡振动而打开，而当直径不当时，则会随着惯性空化而打开。因此，气泡可能必须与毛细血管壁接触才能在没有 IC 的情况下诱导 BBB 开放。结果表明，在压力阈值下，通过非线性气泡振动可以安全地诱导 BBB 开放，其体积高度依赖于声压和气泡直径。
